rs11913319

Positions:

• chr22-19880016-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006440.5(TXNRD2):​c.1275+163G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,168 control chromosomes in the GnomAD database, including 5,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5481 hom., cov: 33)
• Consequence: TXNRD2 NM_006440.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.89

Genes affected

TXNRD2 (HGNC:18155): (thioredoxin reductase 2) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]

TXNRD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-19880016-C-G is Benign according to our data. Variant chr22-19880016-C-G is described in ClinVar as [Benign]. Clinvar id is 678644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNRD2	NM_006440.5	c.1275+163G>C		intron_variant		ENST00000400521.7	NP_006431.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNRD2	ENST00000400521.7	c.1275+163G>C		intron_variant		1	NM_006440.5	ENSP00000383365.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40202 AN: 152050 Hom.: 5479 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40225 AN: 152168 Hom.: 5481 Cov.: 33 AF XY: 0.263 AC XY: 19542 AN XY: 74380

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.271

Alfa AF: 0.278 Hom.: 751

Bravo AF: 0.264

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11913319; hg19: chr22-19867539; COSMIC: COSV68692063;